Comparison of the efficacy and safety of ShuoTong ureteroscopy and flexible ureteroscopy in the treatment of upper ureteral calculi with CT numberical value greater than 1000 HU / 中华泌尿外科杂志

Objective:To compare the clinical efficacy and safety of Shuo Tong ureteroscopy(ST-URS) and flexible ureteroscope(FURS)combined with holmium laser lithotripsy in the treatment of upper ureteral calculi with CT numerical value ≥ 1000 HU.Methods:A retrospective analysis of the clinical data of patients of upper ureteral calculi with CT numberical value≥1000 HU in the First Affiliated Hospital of Xiamen University was made from January 2018 to November 2020.There were 61 cases treated with ShuoTong ureteroscopy holmium laser lithotripsy (ST-URS group), including 45 males and 16 females, with 40 on the left and 21 on the right, age of(48.3±12.7) years, body mass index of(24.7±2.7)kg/m 2, the diameter of stone of(1.50±0.45)cm, and the CT numberical value of(1 288.8±179.0)(1 017-1 738)HU. There were 87 cases were treated with flexible ureteroscopy holmium laser lithotripsy (FURS group), including 58 males and 29 females, with 56 on the left and 31 on the right, age of(48.5±13.0) years, body mass index of(24.1±3.8)kg/m 2, the stone diameter of(1.45±0.40)cm, and the CT numberical value of(1 311.3±188.9)(1 009-1 817)HU. There were no significant differences in gender, age, body mass index, the location of stone, the diameter of stone and the CT numberical value of stone( P>0.05)between the two groups. For ST-URS group, a rigid ureteral channel sheath and standard mirror(F7.5/11.5)were placed under direct vision, exiting the standard mirror, leaving the channel sheath, inserting a lithotripsy mirror(F4.5/6.5)and a holmium laser[Power: 8-30 W(0.4-1.0 J/20-30 Hz)], and withdrawing the stone fragments after crushing the stone by "nibbling method" . For FURS group, a hard ureteroscope(F8/9.8)was used to explore the lesion side of the ureter, inserting a guide wire and placing a soft ureteral sheath, then inserting a flexible ureteroscope(F8)for holmium laser lithotripsy, and useing a stone basket to remove larger stone fragments. Ureteral stent was routinely indwelled after the operation. On the day 1 and 1 month after the operation, imaging examinations were performed to evaluate the stone-free rate. No residual stones or the diameter of stone was ≤0.4 cm and no urinary tract infection or any symptoms were defined as stone free. The operation time, blood loss, success rate of stage Ⅰ ureteral access sheath placement, incidence of postoperative complications, stone-free rate(SFR) at 1 day after operation, SFR at 1 month after operation, postoperative hospital stay and hospitalization costs were compared between the two groups. According to the size of calculi, the 2 groups were divided into 2 subgroups(≥1.5 cm and <1.5 cm)in order to make further analysis. The operation time, stone-free rate(SFR) at day 1 after operation and SFR at 1 month after operation were compared between the two groups. Results:The operation time of the ST-URS group was shorter than the FURS group(40.10 min vs. 49.43 min, P=0.020), and the incidence of postoperative complications was lower than the FURS group[3.28%(2/61)vs. 13.79%(12/87), P=0.031]. The SFR at day 1 after operation was significantly higher than the FURS group[60.7%(37/61)vs. 25.3%(22/87), P<0.01], and the hospitalization cost was lower than that of the FURS group(27 686 yuan vs. 32 281 yuan, P<0.010). There were no significant differences in the blood loss[(4.92±9.51)ml vs.(3.95±6.04)ml, P=0.452], success rate of stageⅠureteral access sheath placement[ 96.7%(59/61)vs. 96.6%(84/87), P=1.000], SFR at 1 month after operation[81.97%(50/61) vs. 75.86%(66/87), P=0.375] and postoperative hospital stay[(2.5±1.4)d vs.(2.4±0.8)d, P=0.543] between the two groups. When the size of calculi was ≥1.5cm, the operation time of the ST-URS group was shorter than the FURS group (43.67 min vs 55.00 min), the SFR at 1 day after operation was higher than the FURS group[40.00%(12/30)vs. 9.38%(3/32)], and the above differences are all statistically significant ( P<0.05). Conclusions:Compared with the FURS, for the treatment of upper ureteral calculi with CT numerical value ≥1000 HU, the ST-URS has shorter in operative time, lower in hospitalization cost and incidence of postoperative complications and higher SFR at day 1 after operation. The ST-URS is a safe and effective surgical technique, which is superior in the treatment of larger(≥1.5 cm) stones.

Association between neutrophil-to-lymphocyte ratio and suicidal ideation in children and adolescents with first-episode depression / 四川精神卫生

BackgroundSuicide is one of the serious public health problems worldwide. The relationship between suicide and neutrophil-to-lymphocyte ratio （NLR） may vary in different regions and different age. It is necessary to further investigate the relationship between NLR and suicidal ideation in Chinese children and adolescents with depression. ObjectiveTo explore the correlation between NLR and suicidal ideation in children and adolescents with depression， so as to provide clues for exploring the biomarkers of suicide. MethodsA retrospective analysis of 536 children and adolescents with depression who were hospitalized in the Third People's Hospital of Fuyang from January 2020 to December 2022 and met the diagnostic criteria of the International Classification of Diseases， tenth edition （ICD-10） was performed. Patients were divided into two groups according to whether they reported suicidal ideation. Demographic data， discharge diagnosis， Hamilton Depression Scale-17 item （HAMD-17） score and hematological test data （neutrophil counts， lymphocyte counts） on the second day were collected from medical records. Receiver operating characteristic （ROC） curve was used to determine the optimal cut-off point of NLR for predicting suicidal ideation in children and adolescents with depression， and binary Logistic regression was used to analyze the risk factors for suicidal ideation. ResultsAmong the 536 patients， 429 cases （80.04%） had no suicidal ideation， and 107 cases （19.96%） had suicidal ideation. Compared with patients without suicidal ideation， the HAMD-17 score ［（25.28±8.86） vs. （21.21±8.46）， F=19.400， P<0.01］， neutrophil level ［（3.85±1.68）×109/L vs. （3.15±1.14）×109/L， Z=4.073， P<0.01］， and NLR level ［（1.96±1.50） vs. （1.52±0.71）， Z=3.532， P<0.01］ in the suicidal ideation patients were significantly higher. The optimal critical NLR value determined by the ROC curve was 1.52 （59.80% sensitivity， 58.50% specificity）， with an area under the curve of 0.610. Logistic regression analysis showed that the risk of suicidal ideation was 1.94 times higher in those with high NLR than in the low NLR after controlling for age， sex， age at onset， duration of illness， and HAMD-17 score （OR=1.940， 95% CI： 1.251~3.009， P=0.003）. ConclusionNLR may be a risk factor and potential biomarker influencing suicidal ideation in the children and adolescents with first-episode depression. ［Funded by Scientific Research Project of Fuyang Municipal Health Commission （number， FY2020xg14）］

Bayesian network analysis of open, laparoscopic, and robot-assisted radical cystectomy for bladder cancer.

BACKGROUND: We have performed the direct and network meta-analysis to evaluate the safety and efficacy of robot-assisted (RARC) versus laparoscopic (LRC) versus open radical cystectomy (ORC) for bladder cancer (BCa). METHODS: A systematic search of PubMed, Cochrane Library, and Embase was performed up until Dec 20, 2019. Outcome indexes include oncologic outcomes (the recurrence rate, mortality), pathologic outcomes (lymph node yield (LNY), positive lymph node (PLN), positive surgical margins (PSM)), perioperative outcomes (operating time (OP), estimated blood loss (EBL), blood transfusion rate, the length of hospital stay (LOS) and the time to regular diet) and postoperative 90-day complications. RESULTS: We have analyzed 6 RCTs, 23 prospective studies, and 25 retrospective studies (54 articles: 6382 patients). On one hand, the direct meta-analysis shows RARC is better than LRC or ORC. On the other hand, the clinical effects of the recurrence rate, Morbidity, PSM, LNY, PLN, and postoperative 90-day complications of RARC, LRC and ORC are all no statistical significance by network meta-analysis. Moreover, the probability rank shows that the comprehensive rank of RARC is better than LRC or ORC. The clinical effects of OP, EBL, LOS, blood transfusion rate and the time to regular diet are all statistical significance by network meta-analysis. There are ORC > LRC > RARC in the EBL ranking. Patients with RARC exhibited a decrease of LOS compared to those with LRC or ORC. Patients with RARC exhibited a decrease in blood transfusion rate and the time to regular diet compared to those with ORC. Patients with ORC exhibited an increase of OP compared to those with RARC or LRC. The heterogeneity tests of most studies are < 50%. Most studies have no publication bias and the quality of the selected studies is good. CONCLUSION: The direct meta-analysis and network meta-analysis suggest that RARC is better than LRC or ORC according to comprehensive analysis. However, we need a large sample size and more high-quality studies to verify and improve in the further.

Urethral meatus stricture BOO stimulates bladder smooth muscle cell proliferation and pyroptosis via IL­1ß and the SGK1­NFAT2 signaling pathway.

Bladder outlet obstruction (BOO), which is primarily caused by benign prostatic hyperplasia, is a common chronic disease. However, previous studies have most commonly investigated BOO using the acute obstruction model. In the present study, a chronic obstruction model was established to investigate the different pathological alterations in the bladder between acute and chronic obstruction. Compared with chronic obstruction, acute obstruction led to increased expression of proliferating cell nuclear antigen and interleukin­1ß, which are markers of proliferation and inflammation, respectively. Furthermore, increased fibrosis in the bladder at week 2 was observed. Low pressure promoted mice bladder smooth muscle cell (MBSMC) proliferation, and pressure overload inhibited cell proliferation and increased the proportion of dead MBSMCs. Further investigation using serum/glucocorticoid regulated kinase 1 (SGK1) small interfering RNAs indicated that low pressure may promote MBSMC proliferation by upregulating SGK1 and nuclear factor of activated T­cell expression levels. Therefore, the present study suggested that acute obstruction led to faster decompensation of bladder function and chronic bladder obstruction displayed an enhanced ability to progress to BOO.

RNA-Binding Protein MSI2 Binds to miR-301a-3p and Facilitates Its Distribution in Mitochondria of Endothelial Cells.

Numerous miRNAs have been detected in mitochondria, which play important roles in many physiological and pathophysiological processes. However, the dynamic changes of miRNA distribution in mitochondria and their mechanisms in reactive oxygen species (ROS)-induced endothelial injury remain unclear. Therefore, miRNA levels in whole cells and mitochondria of H2O2-treated endothelial cells were analyzed by small RNA sequencing in the present study. The results showed that H2O2 significantly reduced the relative mitochondrial distribution of dozens of miRNAs in human umbilical vein endothelial cells (HUVECs). Among the high-abundance miRNAs, miR-301a-3p has the most significant changes in the redistribution between cytosol and mitochondria confirmed by absolute quantitative polymerase chain reaction (qPCR). To unravel the mechanism of miR-301a-3p distribution in mitochondria, RNA pull-down followed by label-free quantitative proteomic analysis was performed, and RNA-binding protein Musashi RNA binding protein 2 (MSI2) was found to specifically bind to miR-301a-3p. Western blotting and immunofluorescence colocalization assay showed that MSI2 was located in mitochondria of various cell types. H2O2 significantly downregulated MSI2 expression in whole endothelial cells, promoted the distribution of MSI2 in cytosol and decreased its distribution in the mitochondria. Moreover, overexpression of MSI2 increased the mitochondrial distribution of miR-301a-3p, whereas inhibition of MSI2 decreased its distribution in mitochondria. Thus, MSI2 might be responsible for the distribution of miR-301a-3p between cytosol and mitochondria in endothelial cells. Our findings revealed for the first time that MSI2 was involved in the regulation of miRNA distribution in mitochondria and provided valuable insight into the mechanism of mitochondrial distribution of miRNAs.

Values of Minimal Apparent Diffusion Coefficient,Difference between Ratios of Apparent Diffusion Coefficients,and Dynamic Contrast-enhanced Magnetic Resonance Imaging Features in Diagnosing Breast Ductal Carcinoma In Situ with Microinvasion / 中国医学科学院学报

To explore the values of minimal apparent diffusion coefficient(ADC),difference between ratios of apparent diffusion coefficients(ADC),and dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)in the treatment of breast ductal carcinoma in situ with microinvasion(DCIS-Mi). Totally 27 patients with DCIS-Mi and 31 patients with breast ductal carcinoma in situ(DCIS)were collected in our hospital from October,2016 to June,2018.Philips Ingenia 3.0T superconducting magnetic resonance scanner and dedicated phase-controlled array surface coil were used for breast examinations.ADC and maximum apparent diffusion coefficient(ADC)were selected from multiple regions of interest(ROI)in the apparent diffusion coefficients(ADC)figure,and ADC was calculated.In addition,DCE-MRI characteristics were analyzed. The ADC of DCIS-Mi was significantly lower than that of DCIS[(1.15±0.03)×10 mm /s .(1.34±0.04)×10 mm /s,=-7.192,=0.002],the ADC was significantly higher than that of DCIS[(0.32±0.03)×10 mm /s .(0.18±0.08)×10 mm /s,=-10.228,<0.001],and the early enhancement rate of DCIS-Mi was higher than that of DCIS[159.71(157.82,162.49)% .147.29(143.59,160.22)%,=-3.578,=0.007].The background parenchymal enhancement of DCIS-Mi was moderate,severe,and non-lump-like,mainly segmental,and the internal enhancement was heterogeneous or clustered circular.Multivariate Logistic regression analysis showed that non-internal characteristics of the mass,the edge of the mass,internal enhancement characteristics of the mass,time-intensity curve,early enhancement rate,ADC and ADC were the optimal variables for the diagnosis of DCIS-Mi,and the optimal variables were shown by receiver operating characteristic(ROC)curve analysis:the area under curve,sensitivity and specificity of ADC,ADC,non-tumor internal enhancement,and tumor internal enhancement were higher,with the critical values being 1.12×10 mm /s,0.31×10 mm /s,1.50,and 1.50,respectively. DCE-MRI combined with ADC value(especially ADC,ADC,non-mass internal enhancement,and mass internal enhancement)is helpful in differentiating breast DCIS-Mi and DCIS.

Altered glutamate metabolism contributes to antiepileptogenic effects in the progression from focal seizure to generalized seizure by low-frequency stimulation in the ventral hippocampus.

As a promising method for treating intractable epilepsy, the inhibitory effect of low-frequency stimulation (LFS) is well known, although its mechanisms remain unclear. Excessive levels of cerebral glutamate are considered a crucial factor for epilepsy. Therefore, we designed experiments to investigate the crucial parts of the glutamate cycle. We evaluated glutamine synthetase (GS, metabolizes glutamate), glutaminase (synthesizes glutamate), and glutamic acid decarboxylase (GAD, a γ-aminobutyric acid [GABA] synthetase) in different regions of the brain, including the dentate gyrus (DG), CA3, and CA1 subregions of the hippocampus, and the cortex, using western blots, immunohistochemistry, and enzyme activity assays. Additionally, the concentrations of glutamate, GABA, and glutamine (a product of GS) were measured using high-performance liquid chromatography (HPLC) in the same subregions. The results indicated that a transiently promoted glutamate cycle was closely involved in the progression from focal to generalized seizure. Low-frequency stimulation (LFS) delivered to the ventral hippocampus had an antiepileptogenic effect in rats exposed to amygdaloid-kindling stimulation. Simultaneously, LFS could partly reverse the effects of the promoted glutamate cycle, including increased GS function, accelerated glutamate-glutamine cycling, and an unbalanced glutamate/GABA ratio, all of which were induced by amygdaloid kindling in the DG when seizures progressed to stage 4. Moreover, glutamine treatment reversed the antiepileptic effect of LFS with regard to both epileptic severity and susceptibility. Our results suggest that the effects of LFS on the glutamate cycle may contribute to the antiepileptogenic role of LFS in the progression from focal to generalized seizure.

Effect of Work Injuries Rehabilitation Investigate System on Early Intervention of Hand Trauma Rehabilitation / 中国康复理论与实践

Objective To establish a management system to promote early rehabilitation for work injured patients. Methods The 2015 hospitalized patients were set as control group (n=16,635), and the 2016 hospitalized patients were set as observation group (n=15,372). The control group was hospitalized for injury data collection surveys and was not implemented systematic rehabilitation propaganda, rehabilita-tion assessment and rehabilitation guidance. However, the observation group hospitalized after establishment of the Work Injuries Rehabilita-tion Investigation System and accepted work injuries rehabilitation intervention, such as rehabilitation propaganda, rehabilitation assessment and rehabilitation guidance. The changes of hand trauma rehabilitation indicators were compared between two groups. Results The rate of work injuries rehabilitation intervention was 80.6%in the observation group. In the observation group, the proportion of the patients who re-ceived early rehabilitation treatment in the designated hospital (56.8%) was significantly higher than that of the control group (17.0%) (χ2=2603.683, P<0.001);the proportion of injured patients who were admitted to the designated work injuries rehabilitation institutions (9.4%) was higher than that of the control group (4.3%) (χ2=285.906, P<0.001). The proportion of patients evaluated as disability in the observation group (17.4%) was significantly less than that of the control group (26.3%) (χ2=235.327, P<0.001). The disability score was significantly lower in the observation group (6.23±1.29) than in the control group (8.26±1.16) (t=68.371, P<0.001). Conclusion The Work Injuries Reha-bilitation Investigation System can promote the early rehabilitation for the hand trauma patients in the designated hospital for work injuries, improve the proportion of hand trauma patients to enter the designated work injuries rehabilitation institutions to receive rehabilitation treat-ment, reduce the proportion of disabled persons, and reduce the degree of disability, effectively promote the overall recovery of patients with hand trauma.

Effect of Work Injuries Rehabilitation Investigate System on Early Intervention of Hand Trauma Rehabilitation / 中国康复理论与实践

Objective To establish a management system to promote early rehabilitation for work injured patients. Methods The 2015 hospitalized patients were set as control group (n=16,635), and the 2016 hospitalized patients were set as observation group (n=15,372). The control group was hospitalized for injury data collection surveys and was not implemented systematic rehabilitation propaganda, rehabilita-tion assessment and rehabilitation guidance. However, the observation group hospitalized after establishment of the Work Injuries Rehabilita-tion Investigation System and accepted work injuries rehabilitation intervention, such as rehabilitation propaganda, rehabilitation assessment and rehabilitation guidance. The changes of hand trauma rehabilitation indicators were compared between two groups. Results The rate of work injuries rehabilitation intervention was 80.6%in the observation group. In the observation group, the proportion of the patients who re-ceived early rehabilitation treatment in the designated hospital (56.8%) was significantly higher than that of the control group (17.0%) (χ2=2603.683, P<0.001);the proportion of injured patients who were admitted to the designated work injuries rehabilitation institutions (9.4%) was higher than that of the control group (4.3%) (χ2=285.906, P<0.001). The proportion of patients evaluated as disability in the observation group (17.4%) was significantly less than that of the control group (26.3%) (χ2=235.327, P<0.001). The disability score was significantly lower in the observation group (6.23±1.29) than in the control group (8.26±1.16) (t=68.371, P<0.001). Conclusion The Work Injuries Reha-bilitation Investigation System can promote the early rehabilitation for the hand trauma patients in the designated hospital for work injuries, improve the proportion of hand trauma patients to enter the designated work injuries rehabilitation institutions to receive rehabilitation treat-ment, reduce the proportion of disabled persons, and reduce the degree of disability, effectively promote the overall recovery of patients with hand trauma.

Effects of Horticultural Training Based on Healing Garden on Hand Function after Operation for Hand Trauma / 中国康复理论与实践

Objective To observe the effect of horticultural training based on healing garden as rehabilitation for post-operation of hand trauma.Methods From January,2015 to December,2016,78 patients with functional disorder after operation for hand trauma were random-ized into control group and observation group equally.All the patients accepted routine rehabilitation,while the observation group accepted horticultural training based on healing garden in addition,for 28 days.They were assessed with Total Active Movement(TAM),Disability of Arm Shoulder and Hand(DASH),and Upper Extremity Function Test(UEFT)before and after treatment.Results The scores of TAM, DASH and UEFT improved in both groups after treatment(t>10.632,P<0.001),and improved more in the observation group than in the con-trol group(t>2.269,P<0.05).Conclusion The horticultural training based on healing garden may promote the recovery of movement of fin-gers,function of hand and upper limbs in patients after hand trauma.

Multipartite entanglement indicators based on monogamy relations of n-qubit symmetric states.

Constructed from Bai-Xu-Wang-class monogamy relations, multipartite entanglement indicators can detect the entanglement not stored in pairs of the focus particle and the other subset of particles. We investigate the k-partite entanglement indicators related to the αth power of entanglement of formation (αEoF) for k ≤ n, αϵ and n-qubit symmetric states. We then show that (1) The indicator based on αEoF is a monotonically increasing function of k. (2) When n is large enough, the indicator based on αEoF is a monotonically decreasing function of α, and then the n-partite indicator based on works best. However, the indicator based on 2 EoF works better when n is small enough.

A sub-threshold dose of pilocarpine increases glutamine synthetase in reactive astrocytes and enhances the progression of amygdaloid-kindling epilepsy in rats.

The prognosis of patients exposed to a sub-threshold dose of a proconvulsant is difficult to establish. In this study, we investigated the effect of a single sub-threshold dose of the proconvulsant pilocarpine (PILO) on the progression of seizures that were subsequently induced by daily electrical stimulation (kindling) of the amygdaloid formation. Male Sprague­Dawley rats were each implanted with an electrode in the right basolateral amygdala and an indwelling cannula in the right ventricle. The animals were randomized into groups and were administered one of the following treatments: saline, PILO, saline+L-α-aminoadipic acid (L-AAA; one dosage tested), PILO+L-AAA, or PILO+L-methionine sulfoximine (three dosages tested). Amygdaloid stimulation and electroencephalography were performed once daily. We performed immunohistochemistry and western blot for glial fibrillary acidic protein and glutamine synthetase (GS). We also assayed the enzymic activity of GS in discrete brain regions. An intraperitoneal injection of a sub-threshold PILO dose enhanced the progression of amygdaloid-kindling seizures and was accompanied by an increase in reactive-astrocyte and GS (content and activity) in the hippocampus and piriform cortex. L-AAA and L-methionine sulfoximine, inhibitors of astrocytic and GS function, respectively, abolished the effect of PILO on amygdaloid-kindling seizures. We conclude that one sub-threshold dose of a proconvulsant may enhance the progression of subsequent epilepsy and astrocytic GS may play a role in this phenomenon. Thus, a future therapy for epilepsy could be inhibition of astrocytes and/or GS.

Simultaneous Determination of Glutamate, Glycine, and Alanine in Human Plasma Using Precolumn Derivatization with 6-Aminoquinolyl-N-hydroxysuccinimidyl Carbamate and High-Performance Liquid Chromatography.

A simple, sensitive and reproducible high-performance liquid chromatography (HPLC) method has been validated for determining concentrations of glutamate, glycine, and alanine in human plasma. Proteins in plasma were precipitated with perchloric acid, followed by derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC). Simultaneous analysis of glutamate, glycine, and alanine is achieved using reversed-phase HPLC conditions and ultraviolet detection. Excellent linearity was observed for these three amino acids over their concentration ranges with correlation coefficients (r)>0.999. The intra- and inter-day precision were below 10%. This method utilizes quality control samples and demonstrates excellent plasma recovery and accuracy. The developed method has been successfully applied to measure plasma glutamate, glycine, and alanine in twenty volunteers.

Simultaneous Determination of Glutamate, Glycine, and Alanine in Human Plasma Using Precolumn Derivatization with 6-Aminoquinolyl-N-hydroxysuccinimidyl Carbamate and High-Performance Liquid Chromatography

A simple, sensitive and reproducible high-performance liquid chromatography (HPLC) method has been validated for determining concentrations of glutamate, glycine, and alanine in human plasma. Proteins in plasma were precipitated with perchloric acid, followed by derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC). Simultaneous analysis of glutamate, glycine, and alanine is achieved using reversed-phase HPLC conditions and ultraviolet detection. Excellent linearity was observed for these three amino acids over their concentration ranges with correlation coefficients (r)>0.999. The intra- and inter-day precision were below 10%. This method utilizes quality control samples and demonstrates excellent plasma recovery and accuracy. The developed method has been successfully applied to measure plasma glutamate, glycine, and alanine in twenty volunteers.

Experimental investigation of HGF inhibiting glial scar in vitro.

To study the inhibitory effect of Hepatocyte growth factor (HGF) on the responsive hyperplasia of damaged astrocytes in vitro. We prepared damaged model of astrocytes to simulate the responsive hyperplasia of damaged astrocytes in vivo by culturing astrocytes in vitro; After the first day of Ad-HGF transfection, astrocytes were scratched, then after the first, the third, and the fifth day of scratch, we detect the expression amount of astrocytes specific glial fibrillary acidic protein (GFAP) and the ratio of S-phase cells with flow cytometry, both of which can reflect the proliferation status of damaged astrocytes; After HGF was added in scratched astrocytes, the activity of SPK and MAPK (P42/44) were detected by autoradiography and immunoblotting test; After adding different concentrations of HGF protein in astrocytes cultured in different serum concentrations and adding diverse concentrations of HGF protein, SPK and SPK inhibitor DMS in scratched astrocytes, we detect cell proliferation with 3H-TDR incorporation. The first day after Ad-HGF transfected astrocytes were scratched, the amount of GFAP secreted by astrocytes were decreased significantly (P < 0.05), and the cells in S phase were declined obviously. HGF has bidirectional regulation on SPK of scratched astrocytes: increases the SPK activity when HGF in low dose, while inhibits when in high dose. In addition, DMS can block the signal passage; HGF had no effects on MAPK (P42/44) of damaged astrocytes cells. In conclusion, after the transfection of Ad-HGF, it can inhibit the responsive hyperplasia of damaged astrocytes by the means of blocking SPK passage.

Oral paroxetine for premature ejaculation: a randomized controlled study / 中华男科学杂志

<p><b>OBJECTIVE</b>To validate the therapeutic efficacy of paroxetine in the treatment of premature ejaculation (PE).</p><p><b>METHODS</b>Eighty PE patients up to the inclusion criteria were equally randomized to an experimental and a control group. We observed all the patients for 4 weeks and recorded the baseline data on intravaginal ejaculatory latency time (IELT) and sexual satisfaction scores, followed by oral medication of paroxetine at 20 mg/d for the patients in the experimental group and placebo for the controls. Thirty days after the treatment, we again recorded IELT and sexual satisfaction scores of the patients.</p><p><b>RESULTS</b>After the treatment, the experimental group showed significantly prolonged IELT ([5.75 +/- 1.24] min) and increased sexual satisfaction score (6.4 +/- 1.2) as compared with the baseline data ([0.89 +/- 0.21] min and [2.7 +/- 0.9]) (P < 0.01). The control group exhibited no significant differences before and after the medication either in the mean IELT or in sexual satisfaction scores ([1.06 +/- 0.28] min vs [0.97 +/- 0.18] min and 3.6 +/- 1.3 vs 3.1 +/- 1.1, P > 0.05).</p><p><b>CONCLUSION</b>Oral medication of paroxetine at 20 mg/d for 30 days could improve IELT and sexual satisfaction in PE patients.</p>

Human LINE1 endonuclease domain as a putative target of SARS-associated autoantibodies involved in the pathogenesis of severe acute respiratory syndrome.

BACKGROUND: Severe acute respiratory syndrome (SARS) is a disease with a mortality of 9.56%. Although SARS is etiologically linked to a new coronavirus (SARS-CoV) and functional cell receptor has been identified, the pathogenesis of the virus infection is largely unclear. METHODS: The clinical specimens were processed and analyzed using an indirect enzyme-linked immunosorbent assay (ELISA) in-house. Further investigations of target antigen included reviews of phage display technique, rapid amplification of cDNA ends (RACE) technique, protein expression and purification, Western blotting validation, serological and immunohistochemical staining in postmortem tissue. RESULTS: A type of medium or low titer anti-lung tissue antibodies were found in the sera of SARS patients at the early stage of the disease. Human long interspersed nuclear element 1 (LINE1) gene endonuclease (EN) domain protein was one of the target autoantigens and it was aberrantly expressed in the lung tissue of SARS patients. Anti-EN antibody was positive in the sera of 40.9% of SARS patients. CONCLUSIONS: Human LINE1 endonuclease domain was identified as a putative target of SARS-associated autoantibodies, which were presented in the serum of SARS patients and may be involved in the pathogenesis of SARS.

Establishment of a cell model based on FKBP12 dimerization for screening of FK506-like neurotrophic small molecular compounds.

FK506 is an efficient immunosuppressive agent with an increasing number of clinical applications. It has been approved to prevent rejection in transplant patients and be efficacious in several autoimmune diseases. Its immunosuppressive activity results from binding to receptor proteins designated as immunophilins (i.e., FKBP12, FK506 binding protein). Recent studies have suggested that FK506 can promote neurite outgrowth as a 2nd activity. Furthermore, it has been shown that the neurotrophic property of FK506 is independent of its immunosuppressive action. Although the mechanism of its neurotrophic activity has not yet been well elucidated, FKBP12 is identified as a drug target, and much effort has been directed toward the design of FKBP12-binding molecules, which are neurotrophic but non-immunosuppressive, for clinical use. In this present study, the authors constructed a stable cell line, which underwent apoptosis upon treatment by AP20187, a wholly synthesized, cell-permeable dimeric FK506 derivative, based on FKBP12-mBax dimerization. This AP20187-mediated apoptosis was rapidly reversed by the addition of an FKBP12-binding competitor molecule (FK506 or rapamycin), indicating that this cell line might be used to screen FK506 derivatives. Using the screening model, hundreds of synthetic FK506 analogs were analyzed. A promising compound, named N308, was obtained. The results showed that N308 could inhibit AP20187-induced gene-modified target cell apoptosis and elicit augmentation of neurite extension from both cultured PC-12 cells and chicken dorsal root ganglia cultures.

[Screening of the genes of hepatitis B virus e antigen interacting proteins].

OBJECTIVE: To screen and clone the genes in hepatocytes which encode protein that can interact with hepatitis B e antigen(HBeAg) by yeast-two hybridization. METHODS: Recombined HBeAg bait plasmid (pGBKT7-eAg) was transformed into yeast AH l09, followed by mating with yeast Yl87 containing liver cDNA library plasmid in 2 x YPDA medium. Diploid yeast was plated on synthetic dropout nutrient medium (SD/-Trp-Leu-Ade-His) which contains X-a-gal for selecting positive blue clones. Then positive clones were selected and plasmids were prepared and sequenced. Finally, bioinformatics analysis was performed. RESULTS: Totally 245 positive colonies were selected and 101 colonies were sequenced. Through sequences alignment, 6 novel genes and 35 recorded genes were screened. CONCLUSION: Genes of HBeAg interacting proteins have been cloned successfully, which brings some new clues for further studies on the biological functions of HBeAg and the related proteins.

[Detection of autoimmune parameter of SARS patients].

OBJECTIVE: To explore whether autoimmune phenomena exist in SARS patients, and to seek for unusual autoimmune antibodies in SARS patients. METHODS: Autoantibodies against cell nuclei (ANA), autoantibodies against smooth muscles (SMA), autoantibodies against parietal cells (PCA), autoantibodies against heart cells (HRA) were detected by using immunofluorescence, and autoantibodies against live-kidney microsomes (LKM) and anti-M2 antibodies were detected by ELISA in sera taken from 27 SARS patients and 18 healthy controls. Immunofluorescence was used to localize the targets antigens in slides with biochips of lung (monkey) of SARS associated antibodies. RESULTS: ANA, AMA, LKM and SMA were found positive in 3, 1, 1, and 1 of the 27 SARS sera. In 18 healthy control sera, one ANA and one AMA were positive. Statistical analysis showed that there were no difference between two groups in every item detected. Twenty-six of 27 SARS patients and 5 of 18 healthy controls had strongly stained columnar epithelia of the bronchiole, especially the lumen border of the epithelia?the difference between two groups was significant. CONCLUSION: No antibodies against organs but lung were found in SARS patients. There are auto antibodies against lung tissues in sera of SARS patients.